Most mature lymphocytes continuously recirculate between the blood and lymphatic organs (Butcher, E. C., Curr. Top. Microbiol. Immunol. 128:85 (1986)). Lymphocytes leave the blood by recognizing and binding to the vascular endothelial cells. Thereafter, they migrate between the endothelial cells into the surrounding tissues. Lymphocyte trafficking allows the full repertoire of lymphocyte specificities to be available for immune reactions throughout the body, and it also facilitates the cell-cell interactions required for the generation and control of immune responses. Lymphocyte adherence to endothelial cells is dependent on interactions between complementary adhesion molecules expressed on both cell types (Springer, T. A., Nature 346:425 (1990); Stoolman, L. M., Cell 56:907 (1989); Osborn, L., Cell 62:3 (1990); Pober and Cotran, Transplantation 50:537 (1990); Butcher, E. C., Cell 67:1033 (1991)). Under normal conditions, lymphocytes mainly bind to specialized postcapillary venules called high endothelial venules (HEV). Functionally separate lymphocyte-HEV recognition systems mediating lymphocyte migration to peripheral lymph nodes, mucosal lymphoid organs, synovium, skin and lung-associated lymphoid tissues in an organ-specific manner have been described (Butcher, E. C., et al., Eur. J. lmmunol. 10:210 (1980); Jalkanen, S., et al., Science 233:556 (1986); Picker, L. J., et al., Nature 349:796 (1991); Geoffrey, J. S., et al., FASEB J. 2:A667 (1988)). In inflammation, activation of the endothelial cell results in changes of its adhesion molecule status, which largely determines the magnitude and type of leukocyte influx into the affected tissue. Thus, endothelial cell molecules are a key element in controlling the characteristics of local immune response, and obviously, a derailed understanding of the mechanisms regulating lymphocyte traffic and leukocyte extravasation can provide new means to clinically manipulate the inflammatory response.
Since in man the endothelial cell ligands mediating tissue-selective lymphocyte homing are largely unknown, a need exists for the identification of such molecules.